UNIPROT:P01185 - FACTA Search

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Query: UNIPROT:P01185 (vasopressin)
23,126 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The magnocellular neurones of the supraoptic nucleus which synthesize and secrete vasopressin and oxytocin have been commonly regarded as simple "output" neurones in that they receive an input, generate an action potential and in turn release hormone from their terminals in the posterior pituitary. Three lines of evidence are presented which suggest that rat supraoptic nucleus neurons also have axon collaterals which terminate in the hypothalamus close to the nucleus. Small injections of horseradish peroxidase were made directly into the nucleus in hypothalamic slices, allowing visualization of the axons of supraoptic neurones. Collaterals of these axons could be observed in regions both dorsal and dorsolateral to the supraoptic nucleus. In a separate series of experiments, sections of perfusion-fixed hypothalamus were stained for vasopressin and oxytocin using specific antisera. Peptide-containing collaterals of both types were observed near the supraoptic nucleus, in a region similar to that seen after horseradish peroxidase injections. Finally, electrophysiological studies were carried out on hypothalamic slices containing the supraoptic nucleus. A small concentric bipolar stimulating electrode was placed directly into the nucleus and activity of lateral hypothalamic neurones within 0.1-1 mm of the nucleus was recorded. Of 68 neurones studied, 52 were excited by supraoptic stimulation via a synaptic pathway that could be blocked by Ca2+ -free solutions containing 18 mM Mg2+. These studies suggest that supraoptic neurones communicate via axon collaterals with other neurones in the lateral hypothalamus, in addition to their previously well characterised functional role in neurosecretion.
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PMID:Axon collaterals of supraoptic neurones: anatomical and electrophysiological evidence for their existence in the lateral hypothalamus. 632 27

Renin secretion from the juxtaglomerular cell is controlled by numerous receptors, humoral agents, and ions. Recently, a stretch receptor hypothesis has been advanced to suggest that all of these diverse factors control renin secretion by a mechanism initiated by a fall in cytoplasmic Ca2+. This fall in Ca2+ may be achieved by lowering Ca2+ influx, raising Ca2+ efflux, or sequestering Ca2+ into cellular organelles and binding sites. The increased renin secretion observed with low arterial pressure, beta-adrenergic agonists, parathyroid hormone, glucagon, cyclic AMP, prostaglandins, low Ca2+ and Ca2+ ionophore, high Mg2+, and Na+ and Cl- may be explained in this context. On the other hand, the decreased renin secretion observed with high pressure, alpha-adrenergic agonists, some prostaglandins, angiotensin, vasopressin, and high K+ may be explained by a rise in cytoplasmic Ca2+ mediated by an opposite sequence of events. Recent observations suggest that the fall in cytoplasmic Ca2+ sets in motion the transport of renin from its site of storage (granules) or synthesis into the cytoplasmic space and finally across the plasma membrane. Thus although renin is stored in granules, its secretion occurs by a process quite different from exocytosis.
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PMID:Cellular mechanisms of renin secretion. 635 57

Historically, the sodium ion has been given prominence in relation to cardiovascular disease, perhaps to the exclusion of other ions. Recently, other ions, including chloride, potassium, magnesium and calcium have received increasing attention in relation to hypertension, cardiac arrhythmias, and metabolic derangements. Endocrine factors controlling these ions have also received increasing attention; they include classic hormonal actions as well as neurotransmission and paracrine hormonal actions. Studies indicate that control of the renin-angiotensin-aldosterone system resides in cytosolic calcium ion levels in the juxtaglomerular cell, as well as chloride ion and prostaglandins at the macula densa. Renin release is stimulated by hyperpolarisation of the juxtaglomerular cell induced by beta 1-agonists, parathyroid hormone, glucagon, magnesium and low cytosol calcium. Renin release is inhibited by high calcium, potassium and angiotensin II. Subsequent to renin release, hormonal regulation includes stimulation of converting enzyme activity by cortisol and prostaglandin (PGE2). Other hormonal control includes antidiuretic hormone producing dilution of extracellular electrolytes and augmented peripheral resistance. A recently identified natriuretic factor isolated from cardiac atria appears to be a potent diuretic with actions similar to that of frusemide (furosemide). Other electrolytes have received closer scrutiny. Chloride may play a dominant role in renal sodium reabsorption, responding to prostaglandin levels. Calcium has been recognised as a basic regulator of the secretion of such hormones as noradrenaline, renin, and aldosterone. As well, calcium ion changes are the means by which smooth muscle contraction is effected. Parathyroid hormone and vitamin D regulate the level of this ion in the body. In addition, a high dietary calcium intake appears to play a protective role against hypertension, while calcium channel blockers appear to reduce blood pressure. Endocrine systems play a major role in the protection against acute elevations in serum potassium by means of insulin action and adrenergic modulation of extrarenal potassium disposal. Aldosterone is recognised as the delayed regulator of potassium excretion. Magnesium levels fall in hyperaldosteronism, hyperparathyroidism, and diabetic keto-acidosis, as well as in malnutrition states. A coexisting potassium deficiency may be refractory to therapy until hypomagnesaemia is corrected. The integrated action of these hormones and electrolytes are thus of major importance in regulation of the cardiovascular system.
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PMID:Endocrine physiology of electrolyte metabolism. 638 78

The stable prostaglandin analogue 9-deoxo-16, 16-dimethyl-9-methylene-PGE2 (9-methylene-PGE2) was infused intravenously (0.5 ml/min) in the dosage of 20 micrograms/min for 2 h in conscious euhydrated man. The administration of 9-methylene-PGE2 rapidly induced an increase in urine flow (from 1.2 +/- 0.07 to 5.35 +/- 1.07 ml/min) concomitantly with a decrease in urine osmolality (from 827 +/- 40 to 193 +/- 44 mOsm/kg). Parallel to this tubular reabsorption of sodium (Na+), calcium (Ca2+) and magnesium (Mg3+) increased and that of potassium (K+) decreased as shown by a reduction in the clearance for respective ion divided by the clearance of inulin. Apparently the water diuresis was mediated by an inhibition of arginine vasopressin's (AVP) antidiuretic effect. The mechanism behind the increase in renal tubular reabsorbtion of Na+ could possibly be a 9-methylene-PGE2 mediated modulation of the renal aldosterone effect. However the protocol followed did not provide any evidence for this, or any other explanation of the observed renal retention of Na+, Ca2+ and Mg2+. The results reported here indicate that 9-methylene-PGE2 may have a future use as a water diuretic agent in patients suffering from water retention and dilutional hyponatraemia such as seen in the syndrome of inappropriate antidiuretic hormone (AVP) release commonly known as SIADH or Schwartz-Bartter's Syndrome.
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PMID:Water diuretic effect of intravenously administered 9-deoxo-16, 16-dimethyl-9-methylene-PGE2 in conscious man. 654 32

Mg specifically increases the binding of neurohypophyseal peptides to smooth muscle membranes, and has some less well-defined effects on beta-adrenergic and other drug-induced responses of smooth muscle. The requirement of smooth muscle actomyosin for Mg is not significantly higher than that of the striated muscle proteins: maximal Ca activation can be obtained at about 1 mM [Mg2+]. This is comparable to the estimated free Mg2+ concentration in smooth muscle. The total Mg content of smooth muscle is approximately 30-35 mmol/kg dry cell wt, and approximately 50% of this can be removed in Mg-free solution. Mg concentration in mitochondria and in nuclei of rabbit portal anterior mesenteric vein smooth muscle is not significantly different from the cytoplasmic concentration. Mitochondria isolated from vascular smooth muscle have a highly active, energy-dependent Mg transport system. Mitochondria isolated from atherosclerotic bovine arteries contain increased concentrations of Mg and Ca. In the terminal cisternae of frog striated muscle tetanized for 12 s the Mg content is increased by 26 meq/kg dry wt, suggesting that there is an increase in the permeability of the sarcoplasmic reticulum membrane to (or transport of) Mg during tetanus. At this time, 126 meq Ca/kg dry terminal cisternae has been released, and there is a concomitant increase of 46 meq/kg dry wt K. The amount of Ca released during 1.2-s tetanus is sufficient to increase the total (not free) Ca concentration in the fiber by approximately 1 mM; during the slow time course of the tetanus, most of this Ca is expected to exchange for the equivalent amount of Mg bound in resting frog muscle to the Ca/Mg sites on troponin and parvalbumin.
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PMID:Effects and subcellular distribution of magnesium in smooth and striated muscle. 702 93

It has recently been demonstrated that an established cell line from pig kidney, LLC-PK1, is a useful model for the study of vasopressin-sensitive adenylate cyclase (Roy, C., and Ausiello, D. A. (1981) J. Biol. Chem. 256, 3415-3422; Roy, C., Hall, D., Karish, M., and Ausiello, D. A. (1981) J. Biol. Chem. 256, 3423-3427). The present study on the regulation of this enzyme has led to the demonstration of the modulation of vasopressin-stimulated adenylate cyclase by Ca2+-calmodulin. The characteristics of calmodulin regulation were similar to those described for other enzymes: (a) activation required micromolar quantities of free Ca2+; (b) maximal enzyme rates were altered but not the Km for hormone activation; (c) activity was inhibitable by trifluoperazine; and (d) activation was dependent on the Mg2+ concentration. These findings should help to define the mechanisms of action of several agents known to alter vasopressin-sensitive adenylate cyclase and cell Ca2+ content.
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PMID:Regulation of vasopressin-sensitive adenylate cyclase by calmodulin. 727 76

The synthesis of N-acetyl-[2-(O-methyl)tyrosine]arginine-vasopressin [Ac-Tyr(Me)AVP] was undertaken utilizing a combination of the stepwise active ester and fragment condensation methods. Ac-Tyr(Me)AVP is an antagonist of the vasopressor response to vasopressin (pA2 = 7.18 +/- 0.08), devoid of vasopressor agonist activity, and has an antidiuretic potency of 0.026 +/- 0.002 unit/mg, a 15 000-fold decrease over the antidiuretic activity of [2-(O-methyl)tyrosine]arginine-vasopressin. The analogue is also an antagonist of the in vitro uterotonic activity of oxytocin with pA2 values of 7.29 +/- 0.08 in the absence of Mg2+ and 6.73 +/- 0.14 in 0.5 mM Mg2+. This result of Nalpha-acetylation of Tyr(Me)AVP parallels similar results in the oxytocin series and suggests that this substitution should be considered in the design of potential antagonists of the antidiuretic response to vasopressin.
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PMID:N-Acetyl-[2-(O-methyl)tyrosine]arginine-vasopressin, an interesting antagonist of the vasopressor response to vasopressin. 739 38

The area postrema (AP) is a circumventricular organ located on the dorsal surface of the medulla. Substantial evidence suggests that the AP is an important site involved in cardiovascular regulation. Arginine vasopressin (AVP) is thought to act at the AP to increase the sensitivity of the baroreceptor reflex. We have therefore examined the effects of AVP on AP neurons with the use of extracellular single unit recordings in vitro. Coronal medullary brain slices (thickness = 400 microns) were obtained from male Sprague-Dawley rats and maintained in oxygenated artificial cerebrospinal fluid (aCSF). The slices were perfused with AVP (10(-8) to 10(-6) M), and the effect on single AP neurons was recorded. A total of 79 AP neurons was tested of which 50 (63.3%) were excited by AVP and 5 (6.3%) were inhibited, whereas the remaining 24 (30.3%) cells were unaffected. The excitatory effects of AVP were dose dependent: firing rate increased 92.6 +/- 25.8% at 10(-8) M, 289.4 +/- 53.9% at 10(-7) M, and 456.8 +/- 113.1% at 10(-6) M, respectively. We also examined whether these effects of AVP resulted from direct actions of this peptide on AP cells by testing if responses were retained during blockade of synaptic transmission (achieved by perfusion with a low Ca(2+)-high Mg2+ aCSF) in 11 cells excited by AVP. Nine of these cells were excited by AVP during such synaptic blockade. Finally, we demonstrated that the excitatory responses of five AP cells to AVP were all totally abolished by perfusion of slices with aCSF containing the V1 antagonist ([1-beta-mercapto-beta,beta-cyclopentamethylene propionic acid,2-(O-methyl)tyrosine]-Arg8-vasopressin; Peninsula Laboratories, 10(-6) M).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Vasopressin actions on area postrema neurons in vitro. 765 71

We report the solid-phase synthesis of the D-Cys6 analogues of arginine-vasopressin (AVP), peptide 1, of the selective AVP vasopressor (V1a receptor) antagonist [1-(beta-mercapto-beta,beta-pentamethylenepropionic acid),2-O-methyltyrosine]arginine-vasopressin (d(CH2)5[Tyr(Me)2]-AVP, (A)), peptide 2, of the three nonselective antidiuretic/vasopressor (V2/V1a receptor) AVP antagonists d(CH2)5[Tyr(Et)2]VAVP (B), d(CH2)5[D-Tyr(Et)2]VAVP (C), and d(CH2)5[D-Phe2]VAVP (D) (where V = Val4), peptides 3-5, of the nonselective oxytocin (OT) antagonists d(CH2)5-[Tyr(Me)2]OVT (E) and d(CH2)5[Tyr(Me)2,Thr4,Tyr-NH2(9)]OVT (F) (where OVT = ornithine-vasotocin), peptides 6 and 7, and of the selective OT antagonists desGly-NH2,d(CH2)5[Tyr(Me)2,Thr4]OVT (G) and d(CH2)5]D-Trp2,Thr4]OVT (H), peptides 8 and 9. We also present the repeat syntheses of the previously reported d(CH2)5[D-Trp2]AVT (peptide 10) and its D-Cys6 analogue (peptide 11) (where AVT = arginine-vasotocin). Peptides 1-11 were assayed for agonistic and antagonistic activities in in vivo V1a, V2, and oxytocic assays and in in vitro oxytocic assays without and with 0.5 mM Mg2+. With V2 and V1a agonistic potencies of 0.82 and 0.41 units/mg, [D-Cys6]AVP has retained less than 0.3% of the V2 and V1a potencies of AVP. It exhibits no oxytocic activity and is an in vitro OT antagonist. pA2 = 6.67 (no Mg2+); pA2 = 5.24 (0.5 mM Mg2+). By contrast, with one or two exceptions, a D-Cys6/L-Cys6 interchange in antagonists 2-9, although resulting in reductions of antagonistic potencies in all assays for virtually all peptides 2-9 relative to A-H, has been well tolerated. For peptides 2-5, the anti-V2 and anti-V1a pA2 values range from approximately 5.54 to 7.33 and from 7.19 to 8.06, respectively; the range of in vitro anti-OT pA2 values (no Mg2+) is 7.35-7.87; with 0.5 mM Mg2+, the range is 7.24-8.21. Peptides 2 and 4 have in vivo anti-OT pA2s = 6.60 and 7.16, respectively. For peptides 6-9, the range of in vitro anti-OT pA2 values (no Mg2+) is 7.65-7.96; with 0.5 mM Mg2+, the range is 7.41-7.65, and the in vivo anti-OT pA2 values range from 6.85 to 7.33. With an in vivo anti-OT pA2 = 7.33, peptide 6 is equipotent with its parent E. The in vivo anti-OT potencies of peptides 7-9 are significantly reduced relative to those of F-H. The in vitro anti-OT (0.5 mM Mg2+) pA2 values of 10 and 11 are 7.54 and 7.50, both significantly lower than those previously reported.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Effects of a D-Cys6/L-Cys6 interchange in nonselective and selective vasopressin and oxytocin antagonists. 775 99

1. The brain of the locust contains an extraocular photoreceptor (EOP), which provides the major synaptic excitation to the vasopressin-like immunoreactive (VPLI) interneuron of the suboesophageal ganglion. Although the precise location of the EOP remains unknown, its activity can be determined indirectly by intracellular recording from the VPLI neuron. The excitatory drive to the VPLI neuron occurs only in darkness and is absent in the light. 2. The EOP is preferentially sensitive to light of wavelength 494 +/- 7 (SD) nm (blue-green) and has an absorption spectrum characteristic of a rhodopsin-like photopigment. 3. In the presence of high divalent saline (20 mM Ca2+ and Mg2+), the VPLI neuron receives excitatory input in the light. This indicates that the excitatory input to the VPLI neuron is from a tonically active descending input, which normally is inhibited by the light-induced activation of the presynaptic EOP. 4. Stimulation of the connectives while recording the resultant excitatory postsynaptic potential (EPSP) evoked in VPLI shows that the descending input projects beyond the suboesophageal ganglion, extending as far as the metathoracic ganglion. 5. Pharmacological analysis shows that the descending input to the VPLI neuron is cholinergic: acetylcholine (ACh) strongly depolarizes the neuron and eserine, an ACh esterase inhibitor, markedly potentiates the synaptic excitation of the VPLI neuron. 6. Nicotinic and muscarinic receptor antagonists show that the excitation of VPLI consists of two pharmacologically discrete components. Nicotinic ACh receptors mediate a fast depolarization, whereas muscarinic ACh receptors evoke a more sustained depolarization. Accordingly, both a fast and slow depolarization can be evoked selectively in VPLI by direct application of either nicotine or muscarine. 7. Voltage-clamp analysis shows that the fast EPSP evoked current is similar to that produced by nicotine in that it decreases linearly with membrane depolarization. The current associated with the sustained depolarization is similar to that evoked by muscarine, increasing nonlinearly with membrane depolarization. 8. Activity of the descending input, or application of muscarine, lowers the spike-initiation threshold of the VPLI neuron, thereby increasing its excitability. 9. It is concluded that the presence of two ACh receptor subtypes act synergistically to allow continuous activity of the VPLI neuron for sustained periods (i.e., throughout the hours of darkness).
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PMID:Pharmacological analysis of the cholinergic input to the locust VPLI neuron from an extraocular photoreceptor system. 789 95

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